A link to an older (1998) clinical discussion of lupus nephritis. First paragraph:
>>INTRODUCTION
Renal involvement in systemic lupus erythematosus (SLE) is a common disease manifestation and a strong predictor of poor outcome. The prevalence of renal disease in eight large cohort studies consisting of 2649 SLE patients varied from 31 to 65% (1). A recent study analyzed the annual incidence of nephritis in 384 lupus patients followed at the Johns Hopkins Medical Center between 1992-94. The one year incidence of acute renal disease was 10% (2). The general consensus is that 50% of lupus patients will develop clinically relevant nephritis at some time in the course of their illness.
Most patients develop nephritis early in their disease and it is uncommon to have the original onset of renal disease more than ten years after the appearance of SLE. Studies have suggested a mild increase in the proportion of male lupus patients compared to women with renal disease. Asians, African-Caribbeans and African-Americans may have more nephritis than other ethnic groups (3). HLA antigens have been associated with an increased risk of developing nephritis and the HLA-DR2 and HLA-B8 are more associated with the development of lupus renal disease than inheritance of the HLA-DR4 gene (4-6). Polymorphisms of Fc receptors for IgG (FcgammaR) were recently identified as a risk factor, implicating defective handling of circulating immune complexes in the development of renal disease (7).
A detailed discussion of the immunopathogenesis of lupus nephritis is beyond the scope of this chapter. An understanding of the basic etiology, however, is relevant. At least three potentially overlapping, immuno-pathogenic mechanisms are supported by experimental data. First, circulating immune complexes consisting chiefly of DNA and anti-DNA are deposited in the kidney. Resulting complement activation and chemotaxis of neutrophils leads to a local inflammatory process. Second, in situ formation of antigen and antibody complexes may similarly lead to complement activation and leucocyte mediated injury. Third, antibodies against specific cellular targets may produce renal injury. For example, antibodies, such as anti-ribosomal P, may bind to cytoplasmic antigens that have been translocated to the cell membrane with subsequent penetration and disruption of cellular function.
An additional mechanism is observed in SLE patients with the antiphospholipid antibody syndrome. Glomerular thrombosis can result from the hypercoagulability that accompanies antibodies directed against negatively charged phospholipid-protein complexes (e.g. biologic false positive VDRL, anticardiolipin antibodies, and lupus anticoagulant).
The majority of patients with lupus nephritis are anti-double stranded DNA antibody (anti-DNA) positive and rising anti-DNA titers accompanied by hypocomplementemia, most especially decreasing C3, is often a harbinger of active lupus glomerulonephritis. Since different substrates are used (i.e. bacterial DNA in Farr assay, mammalian DNA, such as calf thymus, in ELISA, and protozoan DNA within the kinetoplast organelle in Crithidia lucilae assay) patients may be negative in one but not another assay. Occasionally lupus patients who are genuinely anti-DNA negative develop clinically significant nephritis. This may occur because of antigen excess and inability to detect circulating anti-DNA which is deposited in the kidney. Alternatively, antibodies such as anti-ribosomal P, anti-Ro, or antibodies to C1q may mediate renal disease. <<
[Article briefly mentions 3 promising approaches: anti-C5, anti-CD40L and LJP397.]
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